title: Differential Regulation of MAPK Phosphorylation in the Dorsal Hippocampus in Response to Prolonged Morphine Withdrawal-Induced Depressive-Like Symptoms in Mice.
abstract: Depression is one of the most frequent neuropsychiatric comorbidities associated with opiate addiction. Mitogen activated protein kinase (MAPK) and MAPK phosphatase (MKP) are involved in drug addiction and depression. However, the potential role of MAPK and MKP in depression caused by morphine withdrawal remains unclear. We utilized a mouse model of repeated morphine administration to examine the molecular mechanisms that contribute to prolonged withdrawal induced depressive-like behaviors. Depressive-like behaviors were significant at 1 week after withdrawal and worsened over time. Phospho-ERK (extracellular signal-regulated protein kinase) was decreased and MKP-1 was elevated in the hippocampus, and JNK (c-Jun N-terminal protein kinase), p38 (p38 protein kinase) and MKP-3 were unaffected. A pharmacological blockade of MKP-1 by intra-hippocampal sanguinarine (SA) infusion prevented the development of depressive-like behaviors and resulted in relatively normal levels of MKP-1 and phospho-ERK after withdrawal. Our findings support the association between hippocampal MAPK phosphorylation and prolonged morphine withdrawal-induced depression, and emphasize the MKP-1 as an negative regulator of the ERK phosphorylation that contributes to depression.
authors.affiliation: Methadone Maintenance Treatment Clinic, Xi'an Mental Health Center, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Shi
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Dang
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003863:Depression / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009020:Morphine / Q000009:adverse effects*; D010766:Phosphorylation; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D009020:Morphine; D020928:Mitogen-Activated Protein Kinases